AJP - Heart and Circulatory Physiology, Vol 270, Issue 6 2191-H2196, Copyright © 1996 by American Physiological Society
Systemic vascular effects during acute rejection of lung allografts
H. Schersten, H. D. Tazelaar, A. R. Cale, V. M. Miller and C. G. McGregor
Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Circulating leukocytes activated during rejection of organ allografts could
potentially have generalized effects on systemic blood vessels of the
transplant recipient. Experiments were designed, therefore, to determine
the function of the endothelium and smooth muscle of arteries from
nontransplanted organs in dogs who received single lung transplants. Dogs
underwent single lung allotransplantation and were immunosuppressed for 5
days. Immunosuppression was then withheld for 3 days, allowing rejection to
occur. Dogs were studied at this time (rejecting) or following treatment
for rejection for an additional 6-8 days (treated). Arteries from
unoperated, untreated dogs also were studied to provide baseline responses
of healthy tissue. Rings cut from left circumflex coronary, nonoperated
native pulmonary, and renal arteries were suspended in organ chambers for
measurement of isometric force. Endothelium-dependent relaxations to the
calcium ionophore A23187 were not affected by rejection in any of the
arteries. Contractions to angiotensin I were reduced significantly only in
native pulmonary arteries. Contractions to KCI and endothelin-1 increased
in renal arteries with endothelium during rejection. These contractions in
renal arteries were reduced following treatment of rejection. None of the
responses of the coronary arteries were affected significantly by rejection
of the lung allograft. These results demonstrate that contractions of
arteries in the transplant recipient's native organs are altered during
rejection of lung allografts. The effects are organ specific, may include
production of endothelium-derived contractile factors in renal arteries,
and can be partially reversed by treatment of rejection.
